What is Epithelial Ovarian Cancer?
Ovarian cancer is an illness that generally falls into two categories: epithelial and non-epithelial ovarian cancers. The vast majority of ovarian cancers, more than 95%, are epithelial, meaning that they start from the cells on the surface of the ovaries. Non-epithelial ovarian cancers, including germ cell, sex-cord stromal, and small cell ovarian cancers which make up about 5% of cases. Epithelial ovarian cancers are further divided into different types, like high-grade serous, low-grade serous, clear cell, endometrioid, and mucinous ovarian cancer, each with different characteristics and results.
Ovarian cancer is the number one cause of death among women who have cancer in the reproductive system, and it’s the second most common form of this type of cancer in the United States, as stated by the Centers for Disease Control and Prevention. Worldwide, ovarian cancer is the third most frequently detected gynecological cancer. It is also the fifth leading cause of death from any form of cancer among women in the United States, and the eighth globally. The high mortality rate is mostly due to how hard it is to spot this illness in its early stages and lack of effective screening methods, which often leads to late diagnosis when the disease is advanced. The main risk factor for ovarian cancer is older age, as it’s most common in women who are past menopause.
The evaluation process for a suspected ovarian cancer involves examining the patient’s medical history, conducting imaging tests to get a picture of the mass, and looking for tumor markers that indicate cancer. The diagnosis of ovarian cancer gets confirmed through these methods. Treatment strategies depend on various factors such as other health problems the patient may have, prior treatments, and the specific characteristics of the tumor. Common treatments include surgery to remove as much of the tumor as possible, chemotherapy to kill cancer cells, and targeted therapies which involve drugs designed to attack specific features of cancer cells. Alongside these, doctors also use neoadjuvant treatments, which are therapies given before the main treatment, and heated intraperitoneal chemotherapy, which delivers heated chemotherapy directly into the abdomen. However, despite advances in treatment, ovarian cancer remains a serious disease with a high chance of coming back and causing mortality, highlighting the need for preventive measures, effective monitoring, and new treatments based on a deep understanding of the disease at the molecular level.
What Causes Epithelial Ovarian Cancer?
The exact cause of ovarian cancer is still not entirely known, but there are some factors which have been identified that could make a person more likely to develop it. Some risk factors for ovarian cancer include getting older, starting your period at a young age, starting menopause at an older age, having a family history of ovarian cancer, never having given birth, being overweight, using talcum powder in the genital area, smoking, having endometriosis and using hormone replacement therapy.
Certain factors, such as never having given birth, starting your period at a young age or starting menopause at an older age, all of which increase the number of times a woman ovulates in her lifetime, seem to be linked to a higher risk of ovarian cancer. However, the exact reasons for this are not clear. In addition, health conditions which cause inflammation, like endometriosis and obesity, might also contribute to the development of ovarian cancer due to stress on the body and damage to the DNA.
Having a personal or family history of breast or ovarian cancer is also a significant risk factor. There are certain gene changes, or mutations, which can make a person more likely to develop cancer. These include mutations in the BRCA1 and BRCA2 genes, as well as other genes linked to certain hereditary cancer syndromes.
Furthermore, some recent studies suggest that the most serious type of ovarian cancer, high-grade serous ovarian cancer, might actually start in the fallopian tubes. This is based on changes seen in the tissue at the end of the fallopian tubes in a condition that is known to be a precursor to this type of cancer. Although current methods for screening for ovarian cancer have not been found to be effective overall, some organizations still think that it could be beneficial to offer different types of screenings to those who are at high risk.
On the other hand, some factors have been found to decrease the risk of ovarian cancer. These include taking oral contraceptives (birth control pills), having both fallopian tubes tied or removed through surgery, breastfeeding and multiple pregnancies.
Risk Factors and Frequency for Epithelial Ovarian Cancer
Ovarian cancer is a health concern many women face in their lifetime. Up until the age of 95, about 1.1% of women may develop ovarian cancer. In 2022, in the US alone, over 19,000 new cases of ovarian cancer were identified, and sadly, more than 12,000 women lost their lives to it. The occurrence of different types of ovarian cancer also tends to vary with age. For instance, high-grade serous ovarian cancer is most common in women aged 60 to 65, whereas low-grade endometrioid ovarian cancer is frequent among women aged 45 to 50. Clear-cell ovarian cancer is more seen in women between 55 and 60.
- High-grade serous and low-grade endometrioid cancers are most common in non-Hispanic White women.
- Asian/Pacific Islander women experience clear-cell cancer at a higher rate.
- Non-Hispanic Black women have the lowest rate of all ovarian cancer subtypes.
Chances of survival and risk of the cancer coming back depend greatly on the stage at which the disease is diagnosed. More than half the patients diagnosed with ovarian cancer already have cancer that has spread to other parts of the body. The patients diagnosed early have a 5-year survival rate of 93.1%, which drops to 30.8% if the disease is in an advanced stage. The risk of cancer coming back is less than 10% for stage I, but as high as 90% for women with stage IV ovarian cancer.
Signs and Symptoms of Epithelial Ovarian Cancer
Ovarian cancer often presents with fairly common and non-specific symptoms, which can make it difficult to diagnose. These symptoms can include:
- Feeling of fullness in the abdomen
- Bloating
- Nausea
- Belly extended or puffed out
- Feeling full quickly when eating
- Tiredness or fatigue
- Changes in bowel habits
- Urinary symptoms, like frequent urination
- Back pain
- Pain during sex
- Weight loss
Abnormal bleeding from the uterus is not common with ovarian cancer. Symptoms might not show up or be mild in the early stages of the disease. Therefore, doctors may miss early signs of ovarian cancer, because the symptoms could be due to other health conditions.
During a physical exam, doctors might listen to your lungs, and check your breasts and abdomen by touching those areas. They also might do an internal exam to check for bumps or changes in your vagina or rectum. They could also check for swollen lymph nodes in your neck, under your arms, and near your groin. If they find anything abnormal, like a hard, bumpy mass or access fluid in your abdomen, they will order more tests.
In advanced cases, ovarian cancer might cause visible changes like a swollen belly, trouble breathing due to fluid in the lungs, or even a firm bump near the belly button from cancer spreading. There are also signs that can show up on the skin, like a sudden increase in a certain type of skin growth, that could suggest “hidden” or occult cancer.
Paraneoplastic syndromes, or health conditions triggered by an immune response to cancer, can sometimes be linked to ovarian cancer. These syndromes can cause symptoms like lack of coordination, slurred speech, rapid eye movements, dizziness, double vision, and more. These symptoms often show up before the cancer itself is found. Additionally, higher levels of a certain hormone in the blood can cause high calcium levels, resulting in altered mental status, fatigue, constipation, abdominal pain, and increased thirst and urination.
Testing for Epithelial Ovarian Cancer
When suspected of having ovarian cancer, your doctor may perform several laboratory tests such as complete blood count or metabolic profile. Doctors may recommend genetic testing for certain genes (BRCA1 and BRCA2) to all women with a specific type of ovarian cancer called epithelial ovarian cancer. Some cancers such as clear cell, endometrioid, or mucinous ovarian cancers may also necessitate a specific genetic test known as MMRd molecular testing.
Particularly when you may have a tumor, your doctor might check for substances in your blood known as cancer markers. These include human gonadotropin, alpha-fetoprotein, and carcinoembryonic antigen tumor markers. They can be useful for excluding certain cancers like those found in germ cells and the gastrointestinal tract.
One common cancer marker linked to ovarian cancer is CA-125. It is a protein that is present when ovarian cancer is advanced but may not be detected in early stages. However, this marker can also increase due to other medical conditions such as pregnancy, other types of cancer, and inflammatory diseases which makes relying solely on this marker somewhat limited.
Another protein in the blood, human epididymis protein 4 (HE4), is found in high levels in many ovarian cancer cases. It is also detected in other cancers such as endometrial cancer and lung adenocarcinomas. Compared to CA-125, it can detect ovarian cancer at an earlier stage, but CA-125 has a higher detection rate with advanced cancers.
Several formulas exist that use these tumor markers to calculate the risk of having epithelial ovarian cancer. These methods combine the levels of these markers, ultrasound findings, and whether the patient has gone through menopause. However, these risk calculators may be less accurate than risk estimates based on imaging studies alone.
Moreover, an ultrasound scan done via the vagina is the first imaging technique used to look at an ovarian mass. It helps in distinguishing between benign (non-cancerous) and malignant (cancerous) findings. Some ultrasounds may be inconclusive, requiring further imaging usually with magnetic resonance imaging or MRI. Overdiagnosis of an ovarian mass can lead to unnecessary stress and procedures, but missing a cancer diagnosis can risk worse health conditions. Thus, a system called the Ovarian-Adnexal Reporting and Data System (O-RADS) helps doctors to make proper management decisions based on ultrasound findings.
Further, MRI plays a critical role in characterizing an ovarian mass when the ultrasound findings are ambiguous, or when CA-125 levels are normal. Similar to the ultrasound O-RADS method, there’s a system that uses MRI features to categorize the risk of an adnexal mass being malignant.
Computed tomography or CT scans are typically done before MRI to rule out other diagnoses in patients with non-specific symptoms. Although MRI is usually preferred after an ultrasound due to its superior capability to detect ovarian malignancies. But CT imaging of the abdomen, pelvis, and chest is often done to understand the extent of disease and for planning the surgery. It is favored due to its widespread availability. In certain situations, a positron emission tomography-CT may be considered to understand if the cancer has spread to the lymph nodes or other areas.
Treatment Options for Epithelial Ovarian Cancer
Ovarian cancer affects a lot of women, and often it is detected at an advanced stage, which makes it crucial to start treatment as soon as possible. The best treatment plan for each person depends on a number of factors including what stage the cancer is at, what kind of cancer it is and any other health conditions you might have. Surgery is often the first step taken to confirm the diagnosis, figure out the stage of the cancer, and remove as much of the cancer as possible. This is followed by treatments that target any leftover cancer cells.
Sometimes, if the cancer is at a very advanced stage where it is unlikely to be all removed by surgery, chemotherapy is given before the surgery to try and shrink the cancer. This approach is especially beneficial to younger women with early-stage and low-grade ovarian cancers who still want to have children in the future. A procedure known as ‘fertility-sparing’ surgery enables such women to retain their ability to reproduce while getting treated for ovarian cancer.
During the operation for ovarian cancer, doctors will remove as much of the visible cancer as possible. This is often done by a specialized physician known as a gynecologic oncologist. If complete removal isn’t possible, they aim to leave behind only small bits of cancer smaller than 1 cm. Having less cancer left after surgery gives a better chance for chemotherapy to work.
In the case of women with early-stage ovarian cancers and who want to keep their ability to get pregnant, modified surgical methods can be used while still getting rid of all visible signs of cancer. However, these patients need to be fully aware of the risks of cancer recurrence. People with certain types of ovarian cancers are advised against this type of surgery.
Depending on the stage and nature of the disease, chemotherapy may be given before or after the surgery. Usually, treatments are given in cycles with rest periods in between. Specific drugs are selected based on the individual’s condition.
Along with chemotherapy, targeted therapies have also been found effective in the treatment of ovarian cancer. This includes using drugs developed to directly interfere with specific molecules that are crucial for the growth and survival of cancer cells. These options are taken into consideration for people who have responded well to the initial phase of chemotherapy.
It’s important to note that the best approach to treating ovarian cancer varies from person to person, and what works best depends on various factors, including the patient’s overall health and the specific characteristics of the cancer.
Following treatment, it’s crucial to have regular check-ups to watch for any signs of the cancer coming back. These follow-ups include physical exams, regular blood tests, and periodic imaging tests based on your doctor’s recommendations.
What else can Epithelial Ovarian Cancer be?
When a doctor suspects ovarian cancer, they might also consider similar conditions to rule out. Some of these conditions include:
- Colon cancer
- Embryologic remnants
- Stomach cancer (Gastric adenocarcinoma)
- Cancer that has spread from the gastrointestinal tract (Metastatic gastrointestinal carcinoma)
- Ovarian torsion (a serious condition caused by the ovary twisting)
- Peritoneal cyst (a fluid-filled sac in the abdominal cavity)
- Retroperitoneal mass (a lump in the area behind the abdominal organs)
- Uterine fibroids (noncancerous growths in the uterus)
- Endometriosis (a disorder where tissue similar to the lining of the uterus grows outside of it)
- Papillary adenocarcinoma (a type of cancer typically found in the lungs, but can occur in other parts too)
- Serous adenocarcinomas (a type of cancer typically found in the lining of the lungs, stomach, or intestines)
- Undifferentiated adenocarcinomas (an aggressive type of cancer that doesn’t have a clear origin)
- Small-cell adenocarcinomas (a less common type of lung cancer)
- Brenner tumors (a rare type of ovarian tumor)
What to expect with Epithelial Ovarian Cancer
Ovarian cancer often has a challenging outlook, with fewer than half of patients surviving five years after diagnosis and just around a third making it to the 10-year mark. The outlook for ovarian cancer is strongly tied to the stage of the disease when it’s diagnosed. For example, the survival rate for stage I ovarian cancer can be as high as 70% to 92%, while for stage IV tumors, it’s less than 6%.
Several factors will also affect the outlook, including the patient’s overall health at the start, the type and grade of the cancer, and how much of the cancer is left in the body after the first major surgery to remove the tumor. It’s become clear that the less cancer remains after this first surgery, the better the outlook, which is why guidelines suggest this surgery whenever patients are strong enough to withstand it.
In cases where the disease has spread to nearby tissues, the five-year survival rates go down to 80% and even lower to 25% when the disease has spread to other parts of the body. However, for some patients with recurring disease, another surgery can be an option. Patients whose recurring cancer is in one spot and have less than 500mL of fluid build-up in the abdomen, and those whose recurring cancer still responds to drugs containing platinum, have the best chances from this surgery. That said, recurring tumors that stop responding to platinum-based drugs are usually only given therapy to ease symptoms.
Possible Complications When Diagnosed with Epithelial Ovarian Cancer
Women unable to receive treatment for ovarian cancer often face serious complications like fluid buildup in the abdomen (ascites), blockage of the bowel, fluid in the lung lining (pleural effusion), bladder obstruction, and malnutrition. In the last six months of their lives, women who die from ovarian cancer commonly experience:
- Fatigue or weakness
- Nausea or vomiting
- Constipation
- Swelling in the feet or ankles (pedal edema)
- Anemia
After ovarian cancer treatment, some women deal with health challenges and changes in their daily life. These may involve:
- Depression
- Anxiety
- Nerve Damage (neuropathy)
- Pain in the pelvis
- Fatigue
- Nausea
- Decreased sexual desire
- Pain during sex (dyspareunia)
- Vaginal dryness
Treatment can often affect a woman’s ability to continue working and might cause financial difficulties. Other general side effects from chemotherapy can include:
- Problems with the catheter (tube used to deliver medication)
- Nausea
- Vomiting
- Dehydration
- Abdominal pain
Concerning the medication Bevacizumab, which is used to block the formation of new blood vessels, its adverse effects can include:
- Headache
- Nosebleed (epistaxis)
- High blood pressure
- Protein in the urine (proteinuria)
- Nose inflammation (rhinitis)
- Change in taste
- Dry skin
- Peeling skin (exfoliative dermatitis)
- Bleeding from the rectum
- Abnormal tear production
The most serious side effects that come with a black box warning include gastrointestinal perforation, impaired wound healing, and bleeding. It’s crucial for doctors to inform patients about these complications and the symptoms they should watch for.
Preventing Epithelial Ovarian Cancer
When a patient is diagnosed with ovarian cancer, it’s vital for them to understand their condition and the available treatment options. Specialists such as genetic counselors and cancer doctors should discuss genetic testing with each patient. This testing is particularly important for patients who have inherited conditions that can lead to cancer.
Caring for a patient’s comfort and quality of life is crucial, no matter the stage of the cancer. This includes the involvement of a team of palliative care professionals, who focus on relieving symptoms and reducing suffering, as well as other relevant consultants. They will provide comprehensive care, help in predicting the progression of the disease, and significantly improve the patient’s quality of life. Patients should also be informed about any ongoing research studies that might be relevant to their specific case.
There’s also evidence to suggest that physical activity could reduce the risk of ovarian cancer. Obesity and diabetes have been identified as risk factors for the disease. Recent research has suggested that taking steps to prevent these conditions might also help prevent ovarian cancer.
This is why the American College of Obstetricians and Gynecologists (ACOG) recommends women who show BRCA1 genetic mutations to remove both ovaries and fallopian tubes (a procedure called bilateral salpingo-oophorectomy) by the age of 35 to 40. In women with BRCA2 mutations, this procedure is recommended by the age of 40 to 45. This preventative measure significantly reduces their risk of ovarian cancer.
For women with an average risk of ovarian cancer, it is advised to remove the fallopian tubes (salpingectomy) during other procedures like a hysterectomy (removal of the uterus) or sterilization. This can also help reduce the risk of ovarian cancer.
